tbuckley/cabot-search huggingface dataset:
Recent first report of human-to-dog transmission of Monkeypox virus emphasizes an urgent need of enhancing surveillance and strengthen further explorative research to reveal its real magnitude of reverse zoonosis from other animals including pets as like that happened with SARS-CoV-2 / COVID-19 pandemic – Correspondence
Authors: Ranjit Sah, Vivek Hada, Aroop Mohanty, Najim Z. Alshahrani, Sandip Chakraborty, Manojit Bhattacharya, Chiranjib Chakraborty, Kuldeep Dhama
Journal: International Journal of Surgery (2022)
TEM8 Tri-specific Killer Engager binds both tumor and tumor stroma to specifically engage natural killer cell anti-tumor activity
Authors: Michael F Kaminski, Laura Bendzick, Rachel Hopps, Marissa Kauffman, Behiye Kodal, Yvette Soignier, Peter Hinderlie, Joshua T Walker, Todd R Lenvik, Melissa A Geller, Jeffrey S Miller, Martin Felices
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background The tumor microenvironment contains stromal cells, including endothelial cells and fibroblasts, that aid tumor growth and impair immune cell function. Many solid tumors remain difficult to cure because of tumor-promoting stromal cells, but current therapies targeting tumor stromal cells are constrained by modest efficacy and toxicities. TEM8 is a surface antigen selectively upregulated on tumor and tumor stromal cells, endothelial cells and fibroblasts that may be targeted with specific natural killer (NK) cell engagement. Methods A Tri-specific Killer Engager (TriKE) against TEM8—‘cam1615TEM8’—was generated using a mammalian expression system. Its function on NK cells was assessed by evaluation of degranulation, inflammatory cytokine production, and killing against tumor and stroma cell lines in standard co-culture and spheroid assays. cam1615TEM8-mediated proliferation and STAT5 phosphorylation in NK cells was tested and compared with T cells by flow cytometry. NK cell proliferation, tumor infiltration, and tumor and tumor-endothelium killing by cam1615TEM8 and interleukin-15 (IL-15) were assessed in NOD scid gamma (NSG) mice. Results cam1615TEM8 selectively stimulates NK cell degranulation and inflammatory cytokine production against TEM8-expressing tumor and stromal cell lines. The increased activation translated to superior NK cell killing of TEM8-expressing tumor spheroids. cam1615TEM8 selectively stimulated NK cell but not T cell proliferation in vitro and enhanced NK cell proliferation, survival, and tumor infiltration in vivo. Finally, cam1615TEM8 stimulated NK cell killing of tumor and tumor endothelial cells in vivo. Conclusions Our findings indicate that the cam1615TEM8 TriKE is a novel anti-tumor, anti-stroma, and anti-angiogenic cancer therapy for patients with solid tumors. This multifunctional molecule works by selectively targeting and activating NK cells by costimulation with IL-15, and then targeting that activity to TEM8+ tumor cells and TEM8+ tumor stroma.
Loss of secreted gelsolin enhances response to anticancer therapies
Authors: Kok Haw Jonathan Lim, Evangelos Giampazolias, Oliver Schulz, Neil C Rogers, Anna Wilkins, Erik Sahai, Jessica Strid, Caetano Reis e Sousa
Journal: Journal for ImmunoTherapy of Cancer (2022)

Type 1 conventional dendritic cells (cDC1) play a critical role in priming anticancer cytotoxic CD8+ T cells. DNGR-1 (a.k.a. CLEC9A) is a cDC1 receptor that binds to F-actin exposed on necrotic cancer and normal cells. DNGR-1 signaling enhances cross-presentation of dead-cell associated antigens, including tumor antigens. We have recently shown that secreted gelsolin (sGSN), a plasma protein, competes with DNGR-1 for binding to dead cell-exposed F-actin and dampens anticancer immunity. Here, we investigated the effects of loss of sGSN on various anticancer therapies that are thought to induce cell death and provoke an immune response to cancer. We compared WT (wildtype) with Rag1-/- , Batf3-/- , Clec9agfp/gfp , sGsn-/- or sGsn-/- Clec9agfp/gfp mice implanted with transplantable tumor cell lines, including MCA-205 fibrosarcoma, 5555 BrafV600E melanoma and B16-F10 LifeAct (LA)-ovalbumin (OVA)-mCherry melanoma. Tumor-bearing mice were treated with (1) doxorubicin (intratumoral) chemotherapy for MCA-205, (2) BRAF-inhibitor PLX4720 (oral gavage) targeted therapy for 5555 BrafV600E, and (3) X-ray radiotherapy for B16 LA-OVA-mCherry. We confirmed that efficient tumor control following each therapy requires an immunocompetent host as efficacy was markedly reduced in Rag1-/- compared with WT mice. Notably, across all the therapeutic modalities, loss of sGSN significantly enhanced tumor control compared with treated WT controls. This was an on-target effect as mice deficient in both sGSN and DNGR-1 behaved no differently from WT mice following therapy. In sum, we find that mice deficient in sGsn display enhanced DNGR-1-dependent responsiveness to chemotherapy, targeted therapy and radiotherapy. Our findings are consistent with the notion some cancer therapies induce immunogenic cell death (ICD), which mobilizes anticancer T cells. Our results point to cDC1 and DNGR-1 as decoders of ICD and to sGSN as a negative regulator of such decoding, highlighting sGSN as a possible target in cancer treatment. Further prospective studies are warranted to identify patients who may benefit most from inhibition of sGSN function.
Effect of Cigarette Smoking on Survival of Patients With Angiographically Documented Coronary Artery Disease
Authors: Ronald E. Vlietstra
Journal: JAMA (1986)

Through a multicenter registry of patients in the Coronary Artery Surgery Study, we prospectively evaluated morbidity and mortality in 4,165 smokers with angiographically proved coronary artery disease, 2,675 of whom continued to smoke and 1,490 of whom quit. At five years, mortality (adjusted by Cox analysis for baseline differences) was 22% for those who continued smoking and 15% for quitters. The relative risk (also from the Cox analysis) for mortality in continuers vs quitters was 1.55 (95% confidence interval, 1.29 to 1.85). The adverse effect of smoking mainly took the form of higher frequencies of myocardial infarction-associated death and sudden death: the frequencies of these events during follow-up in continuers vs quitters were 7.9% vs 4.4% for myocardial infarction-associated death and 2.8% vs 1.5% for sudden death. This study supports the recommendation that patients with coronary artery disease should stop smoking. (<i>JAMA</i>1986;255:1023-1027)
Innate cell markers that predict anti-HIV neutralizing antibody titers in vaccinated macaques
Authors: Matthieu Van Tilbeurgh, Pauline Maisonnasse, Jean-Louis Palgen, Monica Tolazzi, Yoann Aldon, Nathalie Dereuddre-Bosquet, Mariangela Cavarelli, Anne-Sophie Beignon, Ernesto Marcos-Lopez, Anne-Sophie Gallouet, Emmanuel Gilson, Gabriel Ozorowski, Andrew B. Ward, Ilja Bontjer, Paul F. McKay, Robin J. Shattock, Gabriella Scarlatti, Rogier W. Sanders, Roger Le Grand
Journal: Cell Reports Medicine (2022)

Given the time and resources invested in clinical trials, innovative prediction methods are needed to decrease late-stage failure in vaccine development. We identify combinations of early innate responses that predict neutralizing antibody (nAb) responses induced in HIV-Env SOSIP immunized cynomolgus macaques using various routes of vaccine injection and adjuvants. We analyze blood myeloid cells before and 24 h after each immunization by mass cytometry using a three-step clustering, and we discriminate unique vaccine signatures based on HLA-DR, CD39, CD86, CD11b, CD45, CD64, CD14, CD32, CD11c, CD123, CD4, CD16, and CADM1 surface expression. Various combinations of these markers characterize cell families positively associated with nAb production, whereas CADM1-expressing cells are negatively associated (p < 0.05). Our results demonstrate that monitoring immune signatures during early vaccine development could assist in identifying biomarkers that predict vaccine immunogenicity.
<scp>RNA</scp> sequencing of single allergen‐specific memory B cells after grass pollen immunotherapy: Two unique cell fates and <scp>CD29</scp> as a biomarker for treatment effect
Authors: Craig I. McKenzie, Nirupama Varese, Pei Mun Aui, Simone Reinwald, Bruce D. Wines, P. Mark Hogarth, Francis Thien, Mark Hew, Jennifer M. Rolland, Robyn E. O'Hehir, Menno C. van Zelm
Journal: Allergy (2022)

Abstract Background Sublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen‐specific IgG 4 . IgG 4 competitively inhibits functional IgE on the surface of effector cells, such as mast cells and basophils, from binding to allergens. To further understand the important role memory B‐cell (Bmem) responses play in mediating the beneficial effects of SLIT, we assessed changes in allergen‐specific Bmem subsets induced by SLIT for grass pollen allergy. Methods Blood samples were collected twice outside the pollen season from twenty‐seven patients with sensitization to ryegrass pollen (RGP; Lolium perenne ) and seasonal rhinoconjunctivitis. Thirteen received 4‐month pre‐seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single‐cell RNA sequencing was performed on FACS‐purified Lol p 1‐specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort. Results Four months of SLIT increased RGP‐specific IgE and IgG 4 in serum and induced two Lol p 1‐specific Bmem subsets with unique transcriptional profiles. Both subsets had upregulated expression of beta 1 integrin ITGB1 (CD29), whereas IGHE (IgE), IGHG4 (IgG 4 ), FCER2 (CD23), and IL13RA1 were upregulated in one subset. There was an increase in the proportion of Lol p 1 + Bmem expressing surface IgG 4 , CD23, and CD29 after SLIT. Conclusions A clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface‐expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects.
Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy
Authors: Pei-Heng Li, Xiang-Yu Kong, Ya-Zhou He, Yi Liu, Xi Peng, Zhi-Hui Li, Heng Xu, Han Luo, Jihwan Park
Journal: Military Medical Research (2022)

Abstract The advent of single-cell RNA sequencing (scRNA-seq) has provided insight into the tumour immune microenvironment (TIME). This review focuses on the application of scRNA-seq in investigation of the TIME. Over time, scRNA-seq methods have evolved, and components of the TIME have been deciphered with high resolution. In this review, we first introduced the principle of scRNA-seq and compared different sequencing approaches. Novel cell types in the TIME, a continuous transitional state, and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer. Thus, we concluded novel cell clusters of cancer-associated fibroblasts (CAFs), T cells, tumour-associated macrophages (TAMs) and dendritic cells (DCs) discovered after the application of scRNA-seq in TIME. We also proposed the development of TAMs and exhausted T cells, as well as the possible targets to interrupt the process. In addition, the therapeutic interventions based on cellular interactions in TIME were also summarized. For decades, quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer. Summarizing the current findings, we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy, which can subsequently be implemented in the clinic. Finally, we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.
Sequence-Based Functional Metagenomics Reveals Novel Natural Diversity of Functional CopA in Environmental Microbiomes
Authors: Wenjun Li, Likun Wang, Xiaofang Li, Xin Zheng, Michael F. Cohen, Yong-Xin Liu
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Exploring the natural diversity of functional genes/proteins from environmental DNA in high throughput remains challenging. In this study, we developed a sequence-based functional metagenomics procedure for mining the diversity of copper (Cu) resistance gene copA in global microbiomes, by combining the metagenomic assembly technology, local BLAST, evolutionary trace analysis (ETA), chemical synthesis, and conventional functional genomics. In total, 87 metagenomes were collected from a public database and subjected to copA detection, resulting in 93,899 hits. Manual curation of 1214 hits of high confidence led to the retrieval of 517 unique CopA candidates, which were further subjected to ETA. Eventually, 175 novel copA sequences of high quality were discovered. Phylogenetic analysis showed that almost all these putative CopA proteins were distantly related to known CopA proteins, with 55 sequences from totally unknown species. Ten novel and three known copA genes were chemically synthesized for further functional genomic tests using the Cu-sensitive Escherichia coli (ΔcopA). The growth test and Cu uptake determination showed that five novel clones had positive effects on host Cu resistance and uptake. One recombinant harboring copA-like 15 (copAL15) successfully restored Cu resistance of the host with a substantially enhanced Cu uptake. Two novel copA genes were fused with the gfp gene and expressed in E. coli for microscopic observation. Imaging results showed that they were successfully expressed and their proteins were localized to the membrane. The results here greatly expand the diversity of known CopA proteins, and the sequence-based procedure developed overcomes biases in length, screening methods, and abundance of conventional functional metagenomics.
Host-mycobiome metabolic interactions in health and disease
Authors: Neelu Begum, Azadeh Harzandi, Sunjae Lee, Mathias Uhlen, David L. Moyes, Saeed Shoaie
Journal: Gut Microbes (2022)

Fungal communities (mycobiome) have an important role in sustaining the resilience of complex microbial communities and maintenance of homeostasis. The mycobiome remains relatively unexplored compared to the bacteriome despite increasing evidence highlighting their contribution to host-microbiome interactions in health and disease. Despite being a small proportion of the total species, fungi constitute a large proportion of the biomass within the human microbiome and thus serve as a potential target for metabolic reprogramming in pathogenesis and disease mechanism. Metabolites produced by fungi shape host niches, induce immune tolerance and changes in their levels prelude changes associated with metabolic diseases and cancer. Given the complexity of microbial interactions, studying the metabolic interplay of the mycobiome with both host and microbiome is a demanding but crucial task. However, genome-scale modelling and synthetic biology can provide an integrative platform that allows elucidation of the multifaceted interactions between mycobiome, microbiome and host. The inferences gained from understanding mycobiome interplay with other organisms can delineate the key role of the mycobiome in pathophysiology and reveal its role in human disease.
The Dispersion of Physicians
Authors: E. Harvey Estes
Journal: JAMA (1982)

In this issue ofThe Journal(p 2392), Newhouse and colleagues demonstrate the rapid geographic diffusion of physicians in most specialties during the period from 1970 to 1979. This demonstration will probably come as no surprise, since it confirms the personal observation of many physicians, who have watched the influx of more and more young colleagues into their communities during the same period, and who have begun to see some of these physicians pull up stakes after a few months and move to other (usually smaller) communities. Newhouse and co-workers have not stopped with the simple demonstration of geographic diffusion. They have analyzed the differing patterns of diffusion among the various specialties and have attempted to understand the forces underlying it. Such understanding is of obvious importance, since it might enable us to predict the choice of location of future physicians, and even to influence such choices. An earlier article
Divergent age patterns of under-5 mortality in south Asia and sub-Saharan Africa: a modelling study
Authors: Andrea Verhulst, Julio Romero Prieto, Nurul Alam, Hallie Eilerts-Spinelli, Daniel J Erchick, Patrick Gerland, Joanne Katz, Bruno Lankoande, Li Liu, Gilles Pison, Georges Reniers, Seema Subedi, Francisco Villavicencio, Michel Guillot
Journal: The Lancet Global Health (2022)
Perioperative management of myeloproliferative neoplasms: A <scp>pan‐Canadian</scp> physician survey and international expert opinion
Authors: Natasha Szuber, Panagiota Toliopoulos, Lambert Busque, Sonia Cerquozzi, Lynda Foltz, Vikas Gupta, Ayalew Tefferi, Alessandro Maria Vannucchi, Christopher Hillis, Brian Leber, Dawn Maze, Jaroslav Prchal, Harold J. Olney, Shireen Sirhan
Journal: American Journal of Hematology (2022)
A multidisciplinary approach to the diagnosis and management of Wilson disease: Executive summary of the 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases
Authors: Michael L. Schilsky, Eve A. Roberts, Jeff M. Bronstein, Anil Dhawan, James P. Hamilton, Anne Marie Rivard, Mary Kay Washington, Karl Heinz Weiss, Paula C. Zimbrean
Journal: Hepatology (2022)

Schilsky, Michael L.; Roberts, Eve A.; Bronstein, Jeff M.; Dhawan, Anil; Hamilton, James P.; Rivard, Anne Marie; Washington, Mary Kay; Weiss, Karl Heinz; Zimbrean, Paula C. Author Information
Contents
Authors: Hilda Capó, César Briceño, Gary Legault, Kristen Nwanyanwu, Sally Baxter, Angela Elam, Victoria Tseng, Tannia Rodriguez, Elise Mike, Alexis Warren, Anne Coleman, Sharon Solomon, Ruth Shoge, Ann Ervin, Melissa Contreras, Joy Harewood, Ugochi Aguwa, Mildred Ba, Fasika Woreta, Lynn Gordon, Rese Knight, Jessica Randolph, Nazlee Zebardast, E Pérez-González
Journal: Ophthalmology (2022)
Prolongation of graft survival via layer-by-layer assembly of collagen and immunosuppressive particles on pancreatic islets
Authors: Phuong Le Tran, Ju-Hyun Kim, Young-Heun Jung, Dong-Cheol Lee, Jeong Uk Choi, Duy Ngoc Le, Joo-Won Nam, Manju Shrestha, Ju-Yeon Kim, Tung Thanh Pham, Jee-Heon Jeong
Journal: Biomaterials (2022)
A Survey on Methods for Predicting Polyadenylation Sites from DNA Sequences, Bulk RNA-Seq, and Single-Cell RNA-Seq
Authors: Wenbin Ye, Qiwei Lian, Congting Ye, Xiaohui Wu
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Alternative polyadenylation (APA) plays important roles in modulating mRNA stability, translation, and subcellular localization, and contributes extensively to shaping eukaryotic transcriptome complexity and proteome diversity. Identification of poly(A) sites (pAs) on a genome-wide scale is a critical step toward understanding the underlying mechanism of APA-mediated gene regulation. A number of established computational tools have been proposed to predict pAs from diverse genomic data. Here we provided an exhaustive overview of computational approaches for predicting pAs from DNA sequences, bulk RNA sequencing (RNA-seq) data, and single-cell RNA sequencing (scRNA-seq) data. Particularly, we examined several representative tools using bulk RNA-seq and scRNA-seq data from peripheral blood mononuclear cells and put forward operable suggestions on how to assess the reliability of pAs predicted by different tools. We also proposed practical guidelines on choosing appropriate methods applicable to diverse scenarios. Moreover, we discussed in depth the challenges in improving the performance of pA prediction and benchmarking different methods. Additionally, we highlighted outstanding challenges and opportunities using new machine learning and integrative multi-omics techniques, and provided our perspective on how computational methodologies might evolve in the future for non-3′ untranslated region, tissue-specific, cross-species, and single-cell pA prediction.
LCK inhibition downregulates YAP activity and is therapeutic in patient-derived models of cholangiocarcinoma
Authors: Caitlin B. Conboy, Jennifer A. Yonkus, EeeLN H. Buckarma, Dong-Gi Mun, Nathan W. Werneburg, Ryan D. Watkins, Roberto Alva-Ruiz, Jennifer L. Tomlinson, Yi Guo, Juan Wang, Daniel O’Brien, Chantal E. McCabe, Erik Jessen, Rondell P. Graham, Rogier C. Buijsman, Diep Vu, Jos de Man, Sumera I. Ilyas, Mark J. Truty, Mitesh Borad, Akhilesh Pandey, Gregory J. Gores, Rory L. Smoot
Journal: Journal of Hepatology (2022)
Regulation of microglial physiology by the microbiota
Authors: James Cook, Marco Prinz
Journal: Gut Microbes (2022)

The mammalian gut contains a large, complex community of microorganisms collectively termed the microbiota. It is increasingly appreciated that gut microbes are closely integrated into mammalian physiology, participating in metabolic symbiosis, promoting immune function and signaling to a wide variety of distant cells, including the brain, via circulating metabolites. Recent advances indicate that microglia, the brain's resident immune cells, are influenced by microbial metabolites at all stages of life, under both physiological and pathological conditions. The pathways by which microbiota regulate microglial function are therefore of interest for investigating links between neurological disorders and gut microbiome changes. In this review, we discuss the effects and mechanisms of microbiota-microglia signaling in steady state, as well as evidence for the involvement of this signaling axis in CNS pathologies.
Lysosomal Ion Channels: What Are They Good For and Are They Druggable Targets?
Authors: Erika Riederer, Chunlei Cang, Dejian Ren
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Lysosomes play fundamental roles in material digestion, cellular clearance, recycling, exocytosis, wound repair, Ca2+ signaling, nutrient signaling, and gene expression regulation. The organelle also serves as a hub for important signaling networks involving the mTOR and AKT kinases. Electrophysiological recording and molecular and structural studies in the past decade have uncovered several unique lysosomal ion channels and transporters, including TPCs, TMEM175, TRPMLs, CLN7, and CLC-7. They underlie the organelle's permeability to major ions, including K+, Na+, H+, Ca2+, and Cl-. The channels are regulated by numerous cellular factors, ranging from H+ in the lumen and voltage across the lysosomal membrane to ATP in the cytosol to growth factors outside the cell. Genetic variations in the channel/transporter genes are associated with diseases that include lysosomal storage diseases and neurodegenerative diseases. Recent studies with human genetics and channel activators suggest that lysosomal channels may be attractive targets for the development of therapeutics for the prevention of and intervention in human diseases.